5α-reductase inhibitors (finasteride and dutasteride) are used to treat benign prostatic hyperplasia (BPH), a common condition that can lead to urinary retention (inability to voluntarily urinate). These drugs reduce prostate size, the risk of acute urinary retention and need for surgical intervention in men with BPH. 5α-reductase inhibitors are used to treat chronic urinary retention as the onset of action is slow; treatment for at least six months may be necessary to assess whether a beneficial response has been achieved. Thereafter, treatment should be continued long term. Combination Therapy: Dutasteride is available as a combination product with tamsulosin. Tamsulosin is an alpha1-adrenoceptor blocker which is another option to treat urinary retention. The following article will describe the mechanism of action, cautions and contraindications, side effects and clinically significant interactions for 5α-reductase inhibitors. Mechanism Of Action In BPH, enlargement of the prostate gland is dependent upon the conversion of testosterone to more potent androgen dihydrotestosterone (DHT) within the prostate. DHT is a male sex hormone that can cause the prostate to grow. 5α-reductase inhibitors block the enzyme 5α-reductase, preventing this conversion and leading to a reduction in prostate volume over time. Drug Enzyme Inhibition Profile Finasteride Selective, competitive inhibitor of Type II 5α-reductase Dutasteride Inhibits Type I and Type II 5α-reductase isoenzymes Created in BioRender. Boucher, M. (2025) https://BioRender.com/afmd9nk Fig 1: 5α reductase inhibitors: mechanism of action Pharmacokinetics Parameter Finasteride Dutasteride Formulation Standard-release tablet Standard-release capsule Bioavailability (F) ~80% ~60% Tmax ~2 hours 1–3 hours Metabolism Primarily via CYP3A4 but no clinically significant drug interactions Primarily via CYP3A4 and CYP3A5 Elimination route Dual renal and faecal Mainly hepatic; minimal renal excretion Half-life 5-6 hours 3–5 weeks Effect of hepatic impairment No data available ↑ Plasma levels and prolonged half-life — use with caution Effect of renal impairment No adjustment required as faecal excretion increases commensurate to the decrease in urinary excretion of metabolites No clinically significant accumulation Cautions And Contraindications The following cautions and contraindications should be noted for 5α-reductase inhibitors Cautions Contraindications Decrease in prostate specific antigen (PSA)* concentrations by approximately 50% in patients with BPH, even in the presence of prostate cancer. Occurs within the first months of therapy, after which time PSA levels stabilise to a new baseline In patients treated with finasteride or dutasteride for six months or more, PSA values should be doubled for comparison with normal ranges in untreated men Total serum PSA levels return to baseline within 6 months of discontinuing treatment Breast cancer has been reported in men treated with finasteride and dutasteride Psychiatric symptoms e.g. depression and suicidal ideation can occur Mild to moderate hepatic impairment (dutasteride) Cardiac failure (dutasteride and tamsulosin combination therapy) Finasteride in pregnancy (including handling tablets) May cause abnormalities of the external genitalia of a male fetus when administered to a pregnant woman Dutasteride in women and children (including handling tablets as dutasteride is absorbed through the skin) Dutasteride and severe hepatic impairment *PSA is a protein produced by normal cells in the prostate and also by prostate cancer cells. PSA levels are often raised in prostate cancer and in enlarged prostate (as patients get older and the prostate gets larger). Adverse Effects Created in BioRender. Boucher, M (2025) https://BioRender.com/t0x9zvg Fig 2: Adverse effects of 5a reductase inhibitors Interactions Dutasteride Long-term coadministration with potent CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, clarithromycin) may increase plasma levels and prolong half-life. Consider reducing dosing frequency if adverse effects occur Finasteride has no found clinically significant drug interactions References https://www.medicines.org.uk/emc/product/547/smpc#gref https://www.medicines.org.uk/emc/product/8988/smpc#gref Do you think you’re ready? Take the quiz below Pro Feature - Quiz 5-Alpha-Reductase Inhibitors Question 1 of 3 Submitting... Skip Next Rate question: You scored 0% Skipped: 0/3 More Questions Available Upgrade to TeachMePharmacy Pro Challenge yourself with over 2100 multiple-choice questions to reinforce learning Learn More Rate This Article